The palladium-catalyzed vinylation of organic halides provides a very convenient method for forming carbon-carbon bonds at unsubstituted vinylic positions. The reaction, reported by Heck (Palladium Reagents in Organic Synthesis, Academic Press, Canada 1985) can be used to prepare fine organics, pharmaceuticals, and specialty monomers. For example, the reaction allows a one-step synthesis of substituted styrenes from aryl bromides and is an excellent method for preparation of a wide variety of styrene derivatives. Heitz et al., Makromol. Chem., 189, 119 (1968).
Vinyl toluenes have been reported as the product of a homogeneous palladium-catalyzed coupling of ethylene with bromotoluenes. The reaction is performed in a two-phase solvent system composed of N,N-dimethyl formamide and water. R. A. DeVries et al., Organometallics, 13, 2405 (1994).
U.S. Pat. Nos. 5,136,069 and 5,243,068 to R. A. DeVries et al. describe preparation of vinylically-unsaturated compounds by reaction of a halogenated organic compound with a hydrolytically-stable, vinylically-unsaturated precursor compound in the presence of (a) a homogeneous zerovalent palladium catalyst complex, (b) an inorganic hydrogen halide acceptor and (c) a diluent which is either water or an aqueous solution containing up to 95% by volume of organic solvent.
Arylation of propylene, ethylene, styrene, and methyl acrylate with iodobenzene was found to be catalyzed by metallic palladium in methanol to give methylstyrene, styrene, t-stilbene, and methyl cinnamate, respectively. Their yields and selectivities increased significantly by the addition of excess potassium acetate as an acceptor of hydriodic acid formed. Mori et al., Bull. Chem. Soc., Japan, 46, 1505 (1973).
A variety of styrene derivatives and 3-vinylpyridine were prepared in moderate to good yields by the palladium-tri-o-tolylphosphine catalyzed reaction of ethylene with aryl bromides or 3-bromopyridine, respectively. (Plevyak et al., J. Org. Chem., 43, 2454 (1970).
Alper et al. in J. Chem Soc. Chem. Comm., 1983, 1270-1271, discloses that alkenes can react with carbon monoxide, water, hydrochloric acid and a mixture of palladium and copper to produce the hydracarbonylated branched chain carboxylic acid. Oxygen is necessary to succeed in the reaction.
A process for preparing the branched chain carboxylic acid, ibuprofen, is described in Japanese Patent Application (Kokai) No. 59-10545 (Mitsubishi Petrochemical, published January, 1984), which teaches that ibuprofen can be prepared by reacting p-isobutylstyrene with carbon monoxide and water or an alcohol in the presence of a palladium(II) catalyst and a peroxide, e.g., cumyl hydroperoxide.
A process for preparing aryl substituted aliphatic carboxylic acids or their alkyl esters is disclosed in U.S. Pat. No. 5,315,026. A 1-aryl substituted olefin is reacted with carbon monoxide in the presence of water or an alcohol at a temperature between about 25.degree. C. and about 200.degree. C. A mixture useful as a catalyst is a palladium compound and a copper compound with at least one acid-stable ligand. Ligands which may be used include monodentate or multidentate electron-donating substances such as those containing elements P, N, O and the like, and those containing multiple bonds such as olefinic compounds. Examples of such acid-stable ligands are trihydrocarbylphosphines, including trialkyl- and triarylphosphines, such as tri-n-butyl-, tricyclohexyl-, and triphenylphosphine; lower alkyl and aryl nitriles, such as benzonitrile and n-propionitrile; ligands containing pi-electrons, such as an allyl compound or 1,5-cyclooctadiene; piperidine, piperazine, trichlorostannate(II), and acetylacetonate; and the like.
U.S. Pat. No. 5,536,870 describes the preparation of substituted olefins by the palladium-catalyzed coupling of vinyl or substituted vinyl compounds with organic halides, and also the formation of carboxylic acids and esters from such substituted olefins. The substituted olefinic compounds are formed by reacting an organic halide with a vinyl or substituted vinyl compound in the presence of a catalytically effective amount of palladium or a salt of palladium having a valence of 1 or 2, and a tertiary phosphine ligand such as neomenthyldiphenylphosphine. This reaction is carried out in the presence or absence of a solvent such as acetonitrile, tetrahydrofuran, dioxane, or dimethylformamide. An important utility of the substituted olefins formed in this manner is the subsequent conversion of such substituted olefins to carboxylic acids or derivatives thereof such as salts or esters (e.g., profen compounds) by carbonylation with carbon monoxide using catalytic systems and reaction conditions described in U.S. Pat. No. 5,536,870.
Despite the above and other technological developments in the field, a need exists for a new, economical, commercially feasible way of producing various arylalkylcarboxylic and/or substituted arylalkylcarboxylic acids on an industrial scale whereby complex reaction mixtures can be efficiently separated into the desired component mixtures without need for excessive capital investment or tedious, time-consuming operations.
Palladium catalysts and tertiary phosphine ligands which have been found effective as catalyst components in the preparation of arylalkylcarboxylic acids and substituted arylalkylcarboxylic acids such as profen-type pharmaceuticals are quite expensive. While U.S. Pat. No. 5,055,611 describes an effective way of recovering and regenerating a carbonylation catalyst used in the preparation of ibuprofen, the process requires a reduced pressure distillation in order to separate the ibuprofen from the carbonylation residue. Reduced pressure distillation when conducted on a plant scale is an expensive and capital-intensive operation. Moreover, there are practical limitations and economic constraints on the materials which can be separated and recovered by reduced pressure distillation. In particular, polycyclic substituted arylalkylcarboxylic acids, such as racemic 2-(6-methoxy-2-naphthyl)propionic acid, .alpha.-dl-2-(3-phenoxyphenyl)propionic acid; and 2-(3-benzoylphenyl)propionic acid, have significantly higher boiling points than ibuprofen. Thus separating such substances from catalyst residues, if possible by reduced pressure distillation, would require special equipment and operating conditions, e.g., high vacuum, wiped film evaporators, etc. Also under the conditions needed for such operations, the possibility exists for some product and/or catalyst component losses to be encountered. Thus a need exists for an efficient way of separating arylalkylcarboxylic acids and/or substituted arylalkylcarboxylic acids, especially substituted arylalkylcarboxylic acids having more than one aromatic ring in the molecule, from expensive residual catalyst components used in their preparation, which does not require reduced pressure distillation with its attendant high investment and operating costs, and which provides an active organic-soluble catalyst residue for reuse via recycle without need for regenerating such residue.
This invention makes it possible to effectively fulfill each of the above-identified needs.